title: Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Küster-Hauser syndrome).
abstract: In a collaborative study, we investigated four 46,XX adolescent girls with Mayer-Rokitansky-Küster-Hauser syndrome and hyperandrogenism. Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T). Functional studies revealed partial repression of steroidogenic enzymes (normal repression of HSD3B2) contrasting with the abnormal reexpression of CYP17A1 enzyme in the OVCAR3 cell line. This fourth new WNT4 mutation confirms that this signaling molecule is involved in mullerian development and androgen biosynthesis repression in the ovary. Interestingly, this mutant partially lacks the capability to repress ovarian steroidogenic enzymes, with abnormal expression of 17α- hydroxylase.
authors.affiliation: Service d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier and Université Montpellier 1, Montpellier, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Philibert
authors.forename: Anna
authors.initials: A
authors.lastname: Biason-Lauber
authors.forename: Iva
authors.initials: I
authors.lastname: Gueorguieva
authors.forename: Chantal
authors.initials: C
authors.lastname: Stuckens
authors.forename: Catherine
authors.initials: C
authors.lastname: Pienkowski
authors.forename: Béatrice
authors.initials: B
authors.lastname: Lebon-Labich
authors.forename: Françoise
authors.initials: F
authors.lastname: Paris
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D058489:46, XX Disorders of Sex Development / Q000235:genetics / Q000378:metabolism; D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000735:Androstenedione / Q000096:biosynthesis; D045744:Cell Line, Tumor; D000013:Congenital Abnormalities; D004252:DNA Mutational Analysis; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000002:abnormalities; D009095:Mullerian Ducts / Q000002:abnormalities* / Q000378:metabolism; D009154:Mutation; D010053:Ovary / Q000378:metabolism*; D010641:Phenotype; D011375:Progesterone Reductase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019170:Somites / Q000002:abnormalities; D013131:Spine / Q000002:abnormalities; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014599:Uterus / Q000002:abnormalities / Q000378:metabolism; D014621:Vagina / Q000002:abnormalities / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060528:Wnt4 Protein; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D012333:RNA, Messenger; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; D051176:beta Catenin; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019326:17-alpha-Hydroxyprogesterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase